CNS Sarcoidosis and Acthar Gel

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT02298491
• Collaborator: Mallinckrodt (Industry)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 54
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to see if treatment with H.P. Acthar® Gel will result in the improvement and long-term stabilization of clinical and radiographic abnormalities that occur in patients with CNS sarcoidosis. In addition, it will also look at whether treatment will be also associated with improvement in measures of quality of life. The treatment of CNS sarcoidosis involves the use of either corticosteroids such as prednisone or potent immunosuppressive agents such as methotrexate, both which can induce severe long term side effects. The adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone (ACTH), which is available for patient use as H.P. Acthar® Gel. The efficacies of H.P. Acthar® Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been previously studied. In addition, little is known regarding the expression of immune markers in CNS sarcoidosis and the association of such markers with disease activity and response to treatment.

Condition or Disease	Intervention/Treatment	Phase
CNS Sarcoidosis	Drug: H.P. Acthar Gel	Phase 4

Detailed Description

Sarcoidosis is a chronic and frequently progressive systemic disease that affects the central nervous system (CNS) in approximately 5% of patients. The hallmark of the disease is the development of chronic inflammation with formation of non-caseating granulomas that can involve the brain parenchyma and meninges and appear as contrast-enhancing mass lesions on magnetic resonance imaging. The granulomas are primarily comprised of proinflammatory T cells (Th1 cells and Th17 cells) and macrophages which accumulate during the early stages of granuloma formation. The inflammation that is generated by these cells is modulated by anti-inflammatory responses mediated by Th2 cells and regulatory T (Treg) cells that later appear and populate the outer regions of the granuloma. The presence of Treg cells are of particular interest since these cell are also detected in high numbers in peripheral blood and the immune suppression that results may underlie the occurrence of anergy in patients with the disease. The treatment of CNS sarcoidosis involves the use of either corticosteroids or potent immunosuppressive agents, both which can induce severe long-term side effects. The adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone (ACTH), which is available for patient use as H.P. Acthar® Gel. The efficacy of H.P. Acthar® Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been previously examined. In addition, little is known regarding the expression of immune markers in CNS sarcoidosis and the association of such markers with disease activity and response to treatment. These issues, therefore, will be explored in the context of this proposal.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Biomarkers of Disease Activity and Treatment Responses in Patients With CNS Sarcoidosis Treated With H.P. Acthar Gel
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: Nov 1, 2020
• Actual Study Completion Date: Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: H.P. Acthar Gel	Drug: H.P. Acthar Gel; 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12; Other Names: ACTH

Outcome Measures

Primary Outcome Measures

1. Total Number of Lesions [1 year]

   Total number of lesions assessed at 1 year

Secondary Outcome Measures

1. Quality of Life Measures [4 weeks, 6 months and 12 months]

   Change in Patient Determined Disease Steps (PDDS), Montreal Cognitive Assessment (MoCA), Symbol-Digit Modalities Test (SDMT), Short Form -36 Health Survey (SF-36), Work Productivity and Activities Impairment -General Health (WPAI-GH) and Beck Depression Inventory-II (BDI-II) at 4 weeks, 6 months and 12 months relative to baseline

2. Quality of Life Measure [6 months and 12 months]

   Treatment Satisfaction Questionnaire for Medication (TSQM) scores at 4 weeks and change in TSQM scores at 6 months and 12 months versus baseline

Other Outcome Measures

1. Serum and Cerebrospinal Fluid Immune Markers [4 weeks, 6 months and 12 months]

   Change in levels of serum and cerebrospinal fluid immune markers at 4 weeks, 6 months and 12 months versus baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A highly probable diagnosis of sarcoidosis, as determined using the World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG) Sarcoidosis Organ Assessment Instrument (Judson et al., 2014), with involvement not limited to the central nervous system.

• At the time of enrollment, a history of clinical deterioration based on the development of new symptoms or worsening previously present symptoms with confirmation by clinical examination and objective clinical testing.

• If on steroids, on a stable dose of the medication for at least 3 months.

Exclusion Criteria:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland, Baltimore	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore
• Mallinckrodt

Investigators

• Principal Investigator: Horea Rus, University of Maryland, Baltimore

Study Documents (Full-Text)

• Study Protocol - Jul 30, 2014

More Information

Publications

• Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Curr Opin Pulm Med. 2002 Sep;8(5):435-40. Review.
• Arnason BG, Berkovich R, Catania A, Lisak RP, Zaidi M. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis. Mult Scler. 2013 Feb;19(2):130-6. doi: 10.1177/1352458512458844. Epub 2012 Oct 3. Review.
• Co DO, Hogan LH, Il-Kim S, Sandor M. T cell contributions to the different phases of granuloma formation. Immunol Lett. 2004 Mar 29;92(1-2):135-42. Review.
• Judson MA, Costabel U, Drent M, Wells A, Maier L, Koth L, Shigemitsu H, Culver DA, Gelfand J, Valeyre D, Sweiss N, Crouser E, Morgenthau AS, Lower EE, Azuma A, Ishihara M, Morimoto S, Tetsuo Yamaguchi T, Shijubo N, Grutters JC, Rosenbach M, Li HP, Rottoli P, Inoue Y, Prasse A, Baughman RP, Organ Assessment Instrument Investigators TW. The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis. 2014 Apr 18;31(1):19-27.
• Miller DH, Kendall BE, Barter S, Johnson G, MacManus DG, Logsdail SJ, Ormerod IE, McDonald WI. Magnetic resonance imaging in central nervous system sarcoidosis. Neurology. 1988 Mar;38(3):378-83.
• Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Kambouchner M, Valeyre D, Chapelon-Abric C, Debré P, Piette JC, Gorochov G. The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 2006 Feb 20;203(2):359-70. Epub 2006 Jan 23. Erratum in: J Exp Med. 2006 Feb 20;203(2):477.
• Moller DR. Treatment of sarcoidosis -- from a basic science point of view. J Intern Med. 2003 Jan;253(1):31-40. Review.
• Royal W 3rd, Mia Y, Li H, Naunton K. Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J Neuroimmunol. 2009 Aug 18;213(1-2):135-41. doi: 10.1016/j.jneuroim.2009.05.012. Epub 2009 Jun 17.
• Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011 Oct 10;11(11):762-74. doi: 10.1038/nri3070. Review.
• Stern BJ, Aksamit A, Clifford D, Scott TF; Neurosarcoidosis Study Group. Neurologic presentations of sarcoidosis. Neurol Clin. 2010 Feb;28(1):185-98. doi: 10.1016/j.ncl.2009.09.012.
• Stern BJ, Krumholz A, Johns C, Scott P, Nissim J. Sarcoidosis and its neurological manifestations. Arch Neurol. 1985 Sep;42(9):909-17. Review.

• Responsible Party: Horea Rus, Professor of Neurology, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT02298491
• Other Study ID Numbers: HP-00062490
• First Posted: Nov 24, 2014
• Last Update Posted: Apr 9, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Sarcoidosis

Study Results

Participant Flow

Arm/Group Title	H.P. Acthar Gel
Arm/Group Description	H.P. Acthar Gel: 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12
Period Title: Overall Study
STARTED	4
COMPLETED	3
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	H.P. Acthar Gel
Arm/Group Description	H.P. Acthar Gel: 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	46.3
Sex: Female, Male (Count of Participants)
Female	3 75%
Male	1 25%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Total Number of Lesions
Description	Total number of lesions assessed at 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	H.P. Acthar Gel
Arm/Group Description	H.P. Acthar Gel: 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12
Measure Participants	3
Number [lesions]	5

2. Secondary Outcome

Title	Quality of Life Measures
Description	Change in Patient Determined Disease Steps (PDDS), Montreal Cognitive Assessment (MoCA), Symbol-Digit Modalities Test (SDMT), Short Form -36 Health Survey (SF-36), Work Productivity and Activities Impairment -General Health (WPAI-GH) and Beck Depression Inventory-II (BDI-II) at 4 weeks, 6 months and 12 months relative to baseline
Time Frame	4 weeks, 6 months and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Quality of Life Measure
Description	Treatment Satisfaction Questionnaire for Medication (TSQM) scores at 4 weeks and change in TSQM scores at 6 months and 12 months versus baseline
Time Frame	6 months and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Serum and Cerebrospinal Fluid Immune Markers
Description	Change in levels of serum and cerebrospinal fluid immune markers at 4 weeks, 6 months and 12 months versus baseline
Time Frame	4 weeks, 6 months and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year
Arm/Group Title	H.P. Acthar Gel
Arm/Group Description	H.P. Acthar Gel: 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12
All Cause Mortality
	H.P. Acthar Gel
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	H.P. Acthar Gel
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	H.P. Acthar Gel
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.